Respiratory Distress Syndrome, NewbornPhase 1/2AS-02NCT02294630
Aerosolized Surfactant in Neonatal RDS
A Phase 1/2 study testing Surfactant in people with Respiratory Distress Syndrome, Newborn, run by Sood, Beena G., MD, MS at 1 site in United States.
Trial summary
Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Respiratory Distress Syndrome, Newborn
- What is being tested?
- Surfactant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)
- Gestational age of 240/7-366/7 weeks
- Postnatal age ≤ 24 hours
- Clinical diagnosis of RDS based on (i) presence of at least two of the four classic symptoms (need of supplemental oxygen, tachypnea, intercostal retractions or grunting), and (ii) exclusion of other causes of respiratory failure and (iii) Clinician intent to administer surfactant if infant requires intubation
- Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours
- Written informed consent from parent/guardian
Who cannot join
- Previous receipt of surfactant
- Infants with respiratory distress who are unstable and require immediate intubation
- Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)
- Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support
- Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia
- Neuromuscular disorder resulting in respiratory compromise
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Aerosolized Survanta in Neonatal Respiratory Distress Syndrome: Phase I/II Study
Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Interventions that decrease need for intubation and mechanical ventilation like noninvasive ventilation (NIV) including nasal continuous positive airway pressure, high flow nasal cannula or nasal intermittent mandatory ventilation are increasingly being used for initial respiratory support in preterm neonates with RDS to improve outcomes. Aerosolized surfactant delivered during NIV is an innovative and promising concept for the treatment of RDS - retaining the advantages of early surfactant with alveolar recruitment while obviating the risks of intubation and mechanical ventilation. The investigators overall hypothesis is that treatment of RDS with aerosolized surfactant in preterm infants undergoing NIV is safe and feasible and will result in short-term improvement in oxygenation and ventilation. The objective of this proposal is to perform a single-center unblinded Phase II randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. Funding Source - FDA-OOPD.
- Conditions
- Respiratory Distress Syndrome, Newborn
- Being tested
- Surfactant
- Medical subject headings
- Respiratory Distress Syndrome, Newborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurfactantDrug
Also called Survanta
Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
| Study group | Role | What they receive |
|---|---|---|
| Dose Schedule I | Active comparator | Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1 Receives: Drug: Surfactant |
| Dose Schedule II | Active comparator | Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2 Receives: Drug: Surfactant |
| Dose Schedule III | Active comparator | Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1 Receives: Drug: Surfactant |
| Dose Schedule IV | Active comparator | Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2 Receives: Drug: Surfactant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events as a Measure of Safety and Feasibility
Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure
Measured: During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours
Patient Status as Evaluated by Dose Level
Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.
Measured: During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.
Short Term Efficacy as Assessed by Need for Intubation
It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 >0.5 to maintain pulse oxygen saturations 90%-95% for >30 minutes; iv). pH <7.2 on 2 arterial or capillary blood gases taken >30 minutes apart; and v). partial pressure of CO2 (PCO2) of >65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.
Measured: Within 72 hours of study intervention
Secondary outcomes (18)
Blood Gas Parameters - pH
Blood gas pH
Measured: 60±30 minutes after end of study intervention
Blood Gas Parameters - pCO2
Blood gas pCO2.
Measured: 60±30 minutes after end of study intervention
Pulse Oximetry
Transcutaneous Pulse oximetry
Measured: 60±30 minutes after end of study intervention
Vital Signs - Heart Rate
Vital signs included heart rate, respiratory rate and systolic blood pressure
Measured: 60±30 minutes after end of study intervention
Vital Signs - Respiratory Rate
Vital signs included heart rate, respiratory rate and systolic blood pressure
Measured: 60±30 minutes after end of study intervention
Vital Signs - Systolic Blood Pressure
Systolic blood pressure
Measured: 60±30 minutes after end of study intervention
Number of Doses of Surfactant - Aerosolized & Intratracheal
Measured: Within 72 hours of study intervention
Pneumothorax, Pneumomediastinum or Other Air Leak
Measured: Within 72 hours of study intervention
Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention
Changes in cerebral oxygenation from baseline as evaluated at end of study intervention
Measured: During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours
Changes in Surfactant Activity in Gastric Aspirates
Concentration of major surfactant lipid (PC 16:0/16:0)
Measured: During study intervention, expected maximum of approximately 8 hours
Cumulative Duration of Non-invasive and Invasive Ventilation
Cumulative duration of non-invasive and invasive ventilation at discharge
Measured: at discharge
Duration of Supplemental Oxygen, Intensive Care, Hospital Stay
Duration of supplemental oxygen, and hospital stay
Measured: During initial hospital stay, expected <= 120 days
Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds
Age at start of feeds, and age at full enteral feeds presented in days
Measured: During initial hospital stay, expected 1st 2 weeks of life
Need for Blood Transfusions
Number of infants requiring blood transfusions
Measured: During initial hospital stay, expected <= 120 days
Growth Parameters
Weight at discharge
Measured: At 7 days, 28 days, 36 weeks corrected GA and discharge
Morbidities Associated With Prematurity
Grade III \& IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD
Measured: During initial hospital stay, expected <= 120 days
Survival to Hospital Discharge
Survival to hospital discharge
Measured: During initial hospital stay, expected <= 120 days
Survival to Discharge Without Severe Morbidity
Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser
Measured: During initial hospital stay, expected <= 120 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2014 (estimated)
- Study startDec 2014
- Primary completionJul 2019
- Study completionJul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome, NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sood, Beena G., MD, MS
- Responsible party
- Sponsor
- Investigators
- Beena G. Sood, MD, MS, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02294630
- Sponsor's protocol ID
- 1206011023
- Other IDs
- 1R01FD004793-01A1, FD004793
- Acronym
- AS-02
- Status last verified
- Jul 2021
- First submitted
- 12 Nov 2014
- Last updated
- 25 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sood BG, Cortez J, Kolli M, Sharma A, Delaney-Black V, Chen X. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study. Early Hum Dev. 2019 Jul;134:19-25. doi: 10.1016/j.earlhumdev.2019.05.005. Epub 2019 May 20.
PubMed 31121339Sood BG, Thomas R, Delaney-Black V, Xin Y, Sharma A, Chen X. Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial. Pulm Pharmacol Ther. 2021 Feb;66:101986. doi: 10.1016/j.pupt.2020.101986. Epub 2020 Dec 16.
PubMed 33338661
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aerosolized Survanta in Neonatal Respiratory Distress Syndrome: Phase I/II Study
- ClinicalTrials.gov ID
- NCT02294630
- Acronym / sponsor ID
- AS-02 / 1206011023
- Conditions
- Respiratory Distress Syndrome, Newborn
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Sood, Beena G., MD, MS
- Study start
- Dec 2014
- Primary completion
- Jul 2019 (actual)
- Study completion
- Jul 2020 (actual)
- First posted
- 19 Nov 2014 (estimated)
- Results
- Posted 25 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Interventions that decrease need for intubation and mechanical ventilation like noninvasive ventilation (NIV) including nasal continuous positive airway pressure, high flow nasal cannula or nasal intermittent mandatory ventilation are increasingly being used for initial respiratory support in preterm neonates with RDS to improve outcomes. Aerosolized surfactant delivered during NIV is an innovative and promising concept for the treatment of RDS - retaining the advantages of early surfactant with alveolar recruitment while obviating the risks of intubation and mechanical ventilation. The investigators overall hypothesis is that treatment of RDS with aerosolized surfactant in preterm infants undergoing NIV is safe and feasible and will result in short-term improvement in oxygenation and ventilation. The objective of this proposal is to perform a single-center unblinded Phase II randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. Funding Source - FDA-OOPD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Schedule I | Active comparator | Drug: SurfactantSurfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:1 |
| Dose Schedule II | Active comparator | Drug: SurfactantSurfactant dose to be administered as aerosol - 100 mg phospholipid/kg. Surfactant Dilution 1:2 |
| Dose Schedule III | Active comparator | Drug: SurfactantSurfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:1 |
| Dose Schedule IV | Active comparator | Drug: SurfactantSurfactant dose to be administered as aerosol - 200 mg phospholipid/kg. Surfactant Dilution 1:2 |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM)
- Gestational age of 240/7-366/7 weeks
- Postnatal age ≤ 24 hours
- Clinical diagnosis of RDS based on (i) presence of at least two of the four classic symptoms (need of supplemental oxygen, tachypnea, intercostal retractions or grunting), and (ii) exclusion of other causes of respiratory failure and (iii) Clinician intent to administer surfactant if infant requires intubation
- Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours
Key exclusion criteria (6 listed)
- Previous receipt of surfactant
- Infants with respiratory distress who are unstable and require immediate intubation
- Active air leak syndrome (e.g. pneumothorax, pneumomediastinum)
- Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support
- Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SurfactantAlso: SurvantaTwo doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer. | Drug | Dose Schedule I, Dose Schedule II, Dose Schedule III, Dose Schedule IV |
Primary outcome
Number of Participants With Adverse Events as a Measure of Safety and Feasibility
Time frame: During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours
Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure
Patient Status as Evaluated by Dose Level
Time frame: During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.
Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.
Short Term Efficacy as Assessed by Need for Intubation
Time frame: Within 72 hours of study intervention
It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 >0.5 to maintain pulse oxygen saturations 90%-95% for >30 minutes; iv). pH <7.2 on 2 arterial or capillary blood gases taken >30 minutes apart; and v). partial pressure of CO2 (PCO2) of >65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.
18 secondary outcomes
Blood Gas Parameters - pH
Time frame: 60±30 minutes after end of study intervention
Blood Gas Parameters - pCO2
Time frame: 60±30 minutes after end of study intervention
Pulse Oximetry
Time frame: 60±30 minutes after end of study intervention
Vital Signs - Heart Rate
Time frame: 60±30 minutes after end of study intervention
Vital Signs - Respiratory Rate
Time frame: 60±30 minutes after end of study intervention
Vital Signs - Systolic Blood Pressure
Time frame: 60±30 minutes after end of study intervention
Number of Doses of Surfactant - Aerosolized & Intratracheal
Time frame: Within 72 hours of study intervention
Pneumothorax, Pneumomediastinum or Other Air Leak
Time frame: Within 72 hours of study intervention
Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention
Time frame: During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours
Changes in Surfactant Activity in Gastric Aspirates
Time frame: During study intervention, expected maximum of approximately 8 hours
Cumulative Duration of Non-invasive and Invasive Ventilation
Time frame: at discharge
Duration of Supplemental Oxygen, Intensive Care, Hospital Stay
Time frame: During initial hospital stay, expected <= 120 days
Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds
Time frame: During initial hospital stay, expected 1st 2 weeks of life
Need for Blood Transfusions
Time frame: During initial hospital stay, expected <= 120 days
Growth Parameters
Time frame: At 7 days, 28 days, 36 weeks corrected GA and discharge
Morbidities Associated With Prematurity
Time frame: During initial hospital stay, expected <= 120 days
Survival to Hospital Discharge
Time frame: During initial hospital stay, expected <= 120 days
Survival to Discharge Without Severe Morbidity
Time frame: During initial hospital stay, expected <= 120 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31121339Sood BG, Cortez J, Kolli M, Sharma A, Delaney-Black V, Chen X. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study. Early Hum Dev. 2019 Jul;134:19-25. doi: 10.1016/j.earlhumdev.2019.05.005. Epub 2019 May 20.
- Results publication: PubMed 33338661Sood BG, Thomas R, Delaney-Black V, Xin Y, Sharma A, Chen X. Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial. Pulm Pharmacol Ther. 2021 Feb;66:101986. doi: 10.1016/j.pupt.2020.101986. Epub 2020 Dec 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beena G. Sood, MD, MS principal investigator
Wayne State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Surfactant in people with Respiratory Distress Syndrome, Newborn, run by Sood, Beena G., MD, MS at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events as a Measure of Safety and Feasibility (time frame: During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02294630, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.